The present invention relates to topical compositions for treating amino acid based substrates. The topical compositions comprise cosmetic or therapeutic actives that have been bound to a protected thiol which acts as a molecular xe2x80x9chookxe2x80x9d to impart xe2x80x9cpermanentxe2x80x9d benefits to the amino acid based substrates. The amino acid based substrates can include, for example, proteinaceous materials such as keratin, as found in human hair, animal fur, velus hair on skin, finger and toe nails; various animal body parts, such as horns, hooves and feathers; other naturally occurring protein containing materials, such as wool; and synthetic polymers. Of particular interest are compositions which deliver and attach cosmetic actives to human hair.
It is well known in the art that amino-acid based fibers, particularly hair, can be treated with agents that deliver one or more cosmetic benefits, such as conditioning, styling or setting. The conventional cosmetic products which have been known and used commercially have relied upon two key factors: deposition and retention. The cosmetic actives must first be physically deposited onto the hair fiber where the active imparts a benefit to a sufficient degree. Secondly, it is essential that the cosmetic actives be retained on the hair beyond the completion of the treatment. For example, when hair is rinsed to remove unwanted excess composition (e.g., a conditioner) a sufficient amount of the cosmetic active (humectant, moisturizer, etc.) remains bonded to the hair so as to maintain the desired cosmetic benefits.
The bonding of the cosmetic active material to the hair is generally of the nature of physico-chemical intermolecular forces, e.g., physisorption. Such physical forces comprise, for example, hydrogen bonding, electrostatic interactions, van der Waals interactions and the like. As an example, cationic cosmetic agents, generally of the quaternary ammonium type, are known to bond to hair by virtue of the interaction of their cations with anionic amino acid residues within keratin, e.g., glutamic acid, aspartic acid, cysteic acid etc. A major problem, however, with physisorption is the inevitable short lived retention of the cosmetic agent on hair. This is due to the relatively weak physical forces which bind the cosmetic to hair and which are easily disrupted by other treatments, e.g. washing. And, given the frequent need for treating hair, performance retention is difficult to achieve and generally does not last in excess of the period between washes.
One approach that has been disclosed in the art to overcome the above problem to provide truly durable or xe2x80x9cpermanentxe2x80x9d cosmetic benefits to hair that are retained through multiple washes is to utilize molecular xe2x80x9chooksxe2x80x9d to chemically bond cosmetic actives to hair keratin, e.g., chemisorption. Chemisorption results in a permanent juncture that is essentially resistant to physical wear from subsequent washings or physical abrasion. Two conventional approaches to achieve chemisorption comprise the use of either electrophilic reactive moieties or thiol reactive moieties attached to the cosmetic active. Electrophilic reactive moieties are designed to react with thiol functional groups present in hair and thiol reactive moieties are designed to react with electrophilic functional groups within the hair to create a covalent bond.
U.S. Pat. No. 5,523,080 issued to Gough et al. on Jun. 4, 1996, U.S. Pat. No. 5,211,942 issued to Deppert et al. on May 18, 1993, and UK Patent Application GB2197887 published on Jun. 2, 1988, all disclose the use of electrophilic moieties. These electrophilic chemistries include the use of azlactone, (haloalkyl)trialkylammonium salts, and acyl halides. All of these molecular hooks have potential to react with hair via an electrophilic mechanism which necessitates sufficient nucleophilic functional groups present within the keratin structure with which to react to a sufficient degree to achieve the desired durable benefits. For hair, this poses a dilemma in that it is generally known that hair does not naturally possess a sufficient concentration of nucleophilic functional groups under consumer mild conditions to drive the reaction. However, it is also generally known that by chemically reducing the disulfide bonds present within the cystine amino acid residues of hair, in a manner analogous to cold waving, sufficient quantities of nucleophilic cystine residues can be produced. Pre-reduction of hair, to enable the chemical reaction with suitable electrophilic cosmetic actives, is illustrated below in reactions (a) and (b). Ker represents keratin protein, Rxe2x80x94X represents an alkyl halide electrophilic cosmetic active, R represents a cosmetic agent and Xxe2x88x92 is a halide anion such as bromide or chloride. 
While electrophilic cosmetic actives have been demonstrated effective at providing durable cosmetic benefits to hair, the approach has disadvantages that arise from the required pre-reduction step. First, the reduction step is known to be a very harsh chemical process that imparts considerable damage to hair. Second, the effective reducing agents are typically mercaptans of low molecular weight and are odiferous. The pre-reduction process generates unpleasant malodor that remains on the hair for greater than a week time in most instances. Thirdly, in addition to unpleasant malodor and resulting hair damage, the required pre-reduction imparts an additional step to the process with attendant added inconvenience to the user.
U.S. Pat. Nos. 5,087,733 and 5,206,013 both issued to Deppert et al. on Feb. 11, 1992 and Apr. 27, 1993 respectively, as well as U.S. Pat. No. 4,973,475 issued to Schnetzinger and Ciaudelli on Nov. 27, 1990, describe the use of quaternary ammonium thiols which fall under the general class of nucleophilic reactive actives. Such nucleophilic actives are generally intended to react with cystine amino acid residues present within hair via formation of a mixed disulfide covalent linkage as is demonstrated in the chemical equation (c). 
Ker represents keratin and Rxe2x80x94SH represents a suitable nucleophilic active where R is a cosmetic agent and xe2x80x94SH representing a nucleophilic moiety. It is generally known that thiols are the preferred nucleophilic reactive moieties that possess enough reactive strength to chemically bond with the disulfide bond of cystine, Kerxe2x80x94Sxe2x80x94Sxe2x80x94Ker, under safe and mild consumer conditions (e.g., relatively non toxic, less than 120xc2x0 F., pH 2 to 11). Most other prospective nucleophilic molecular handles are either highly toxic (e.g., selenols), or are unreactive under mild conditions (e.g., alkoxides with pKaxcx9c15).
There are two major drawbacks to the use of nucleophilic thiols as reactive moieties to form covalent bonds with keratin. First, thiol nucleophilic moieties are known to be unstable in the presence of air. Atmosphere induced oxidation of the thiols to the corresponding, and unreactive, disulfide as is shown in the following equation (d) where Rxe2x80x94SH represents a suitable nucleophilic cosmetic active R being an alkyl cosmetic agent and xe2x80x94SH representing the nucleophilic moiety: 
Such oxidative deactivation of the nucleophilic thiol moieties severely limits their mode of usage. Thus, nucleophilic thiols are generally not stable enough to be utilized as such in a large majority of current product forms, i.e., re-sealable hair care packages widely used for shampoos, rinse-off conditioners etc. Second, the nucleophilic thiol moiety has very little affinity for hair keratin and has very low aqueous solubility, both of which hinder its performance in generating durable cosmetic benefits, especially when attached to hydrophobic, insoluble cosmetic actives, i.e., hydrocarbon conditioners, in-soluble polymers etc.
Despite major efforts, however, the art has not yet provided molecular xe2x80x9chooksxe2x80x9d that provide durable cosmetic benefits to hair that last beyond twenty shampoos and which do not necessitate the damaging cold waving of hair, i.e. hair reduction, while being oxidatively stable in solution for long term storage in a variety of currently used product forms, e.g., rinse of conditioners, two-in-one shampoos, etc.
The present invention is concerned with topical compositions comprising classes of compounds containing at least one thiol in a protected form, which can be released to provide a xe2x80x94SH or xe2x80x94Sxe2x88x92 group prior or simultaneous to use. These protected thiols are referred to herein as xe2x80x9chooksxe2x80x9d. It is understood that within the scope of this invention that functional thiols as represented herein include both the protonated thiol, Rxe2x80x94SH, and unprotonated thiolate, Rxe2x80x94Sxe2x80x94xe2x88x92.
It has now been discovered that, surprisingly, such xe2x80x9chooksxe2x80x9d, Rxe2x80x94(Sxe2x80x94Pr)m, provide durable cosmetic benefits, when applied to amino-acid based substrates without a damaging cold-waving process, that last beyond twenty shampoos. It has also been discovered that the molecular xe2x80x9chooksxe2x80x9d of the present invention provide improved oxidative stability versus conventional thiols by virtue of the appended protecting moiety to the thiol group that reduces the oxidative susceptibility of the sulfur atom(s). Furthermore, it has been found that these molecular xe2x80x9chooksxe2x80x9d significantly outperform conventional nucleophilic thiol hooks in providing durable cosmetic benefits. While not being bound by theory, the latter observed effect is believed to be due to the unexpected high affinity for keratin provided by certain polarizable electrophilic groups which offer improved solubility and possibly even electrostatic interaction with the charged keratinaceous substrate. Presumably, such greater affinity affords enhanced diffusion and adsorption to the fiber by the cosmetic active enabling greater opportunity for binding.
The xe2x80x98hooksxe2x80x99 of the present invention enable the achievement of durable cosmetic benefits that are resistant to cleansing or shampooing from essentially a non-damaging process that is void of cold waving. The binding of the cosmetic actives provided by these molecular xe2x80x98hooksxe2x80x99 is to such a degree of durability that the measured cosmetic benefits will remain in hair for multiple shampoo cycles, e.g. eight to twenty or more. While not being restricted by theory, it is believed that such a high degree of durability is due to the formation of covalent bonds between the cosmetic active and the keratinaceous substrate.
This bond formation may occur in either of two ways. First, the protected thiol compound can be mixed with a activating release agent to form the free functional thiol, reaction (e). The free thiol will then react with the substrate thereby attaching the functional group, reaction (f).
Rxe2x80x94Sxe2x80x94Pr+Release Agentsxe2x86x92Rxe2x80x94Sxe2x88x92xe2x80x83xe2x80x83(e)
2 Rxe2x80x94Sxe2x88x92+Kerxe2x80x94Sxe2x80x94Sxe2x80x94xe2x86x922 Kerxe2x80x94Sxe2x80x94Sxe2x80x94R+Kerxe2x80x94SHxe2x80x83xe2x80x83(f)
R represents the cosmetic active, Ker represents the keratin protein, S represents sulfur, xe2x80x94SH represents the thiol and Pr represents the protecting group. Based on theory, the above thiol-protecting group bond is broken via some form of activation yielding the reactive unprotected thiol which would then be capable of forming a mixed disulfide with keratin disulfides via nucleophilic displacement. Such activation could be accomplished via hydrolysis or by the action of a nucleophile other than water, either in the substrate itself or in a separate composition. Such hydrolysis or nucleophilic attack can itself be enhanced in several way such as by application of a source of energy or catalysis. This mixing may be done prior to use or simultaneously, during application to the substrate. Where the mixing occurs simultaneously to application, the release of the protecting group occurs in-situ on the substrate.
Surprisingly, it has been found that, alternatively, the formation of the covalent bonds may occur without mixing with a release agent. Direct reaction of certain protected thiol compounds with the hair occurs via the formation of a mixed disulfide with the existing disulfide bonds within keratin as is illustrated below, reaction (g): 
While not being bound to theory, it is believed that the keratin itself could be activating the thiol protecting group bond to enable the observed durable benefits. The resulting free protecting group may or may not undergo decomposition reactions. The byproducts of the activation of the sulfur-heterocyclic bond will usually be removed from the substrate by washing.
The cosmetic agent, R, of the present invention may be monofunctionalized, i.e. the cosmetic active moiety, R, carries a single molecular xe2x80x9chookxe2x80x9d connected to the cosmetic agent via a sulfur-sp3 carbon bond, or it may be bis- or multi-functionalized, i.e. the cosmetic active, R, may carry two or more sp3 electrophiles connected to the cosmetic agent via separate sulfur-sp3 carbon bonds. The latter may be useful for example in achieving a greater degree of chemical bonding of the cosmetic agent to the substrate or for generating bonds between adjacent features of the substrate, e.g. producing a cross-linking effect. The latter may be employed to improve the strength or tensile properties of keratinaceous fibers or for enhancing the degree of hair setting compared with prior art hair methods.
It is understood that within the scope of this invention, numerous potentially and actually tautomeric compounds are involved. Thus, for example, 2-mercaptopyridine (I) exists under known conditions in the pyridine-2-thione tautomer form (II). It is to be understood that when this development refers to a particular structure, all of the reasonable additional tautomeric structures are included. In the art, tautomeric structures are frequently represented by one single structure and the present invention follows this general practice. 
Preferred embodiments of the present invention are related to functional silicone compositions. More specifically, these embodiments are related to functional silicone compositions which are used in the cosmetics industry.
Silicones are widely used in hair care products due to the conditioning benefit that they impart to hair. By modern day technology, the silicone is deposited on hair during the application process but is held only by weak physical forces, such as hydrogen bonding or van der Waals interactions. Because the forces are weak, the benefits of silicone by deposition are short lived. Beneficial conditioning effect can also be caused by treating hair with silanol capped amino-functionalized silicones. These can undergo condensation cure reactions on hair to form somewhat durable films. Generally, conditioning benefits are attributed to the deposition of high molecular weight, high viscosity fluids and gums which can weight down the hair.
It is widely known by those skilled in the art that covalent bonding is the key to xe2x80x9cpermanentxe2x80x9d hair treatment. Processes which alter the structure of the hair, such as permanent wave and color treatment methods, do provide longer lasting effects. These processes include glycolate reduction and peroxide reoxidation. However, the processes are very damaging to hair and can only be carried out every eight to ten weeks.
Gough et al. in U.S. Pat. Nos. 5,523,080 and 5,525,332 describe the synthesis of silicone-azlactone polymers which exhibit covalent bonding and xe2x80x9cpermanentxe2x80x9d conditioning benefit. Gough et al. discuss incorporating an azlactone-functionalized copolymer which consists of vinylazlactone and methacryloyl polydimethylsiloxane monomers into a silicone-active group-hair structure. The hair treatment using the silicone-azlactone polymers did not consist of the steps of reduction with a glycolate or reoxidation with peroxide.
New compositions are constantly being sought which impart improved hair care benefits without a harsh, damaging chemical treatment.
This invention relates to a topical composition for treating amino acid based substrates comprising a protected thiol compound having the formula
Rxe2x80x94(Sxe2x80x94Pr)m
where R is a mono or multivalent cosmetically active functional group, S is sulfur, and Pr is a protecting group, and m is an integer between 1 and 100. The invention further relates to systems which comprise this protected thiol compound and an activating mechanism. The protected thiol compounds of the present invention may be used in hair care compositions, textile care compositions, cosmetic compositions, oral care compositions, skin care, nail care, laundry care, acne care and animal care compositions.
A preferred embodiment of the present invention provides a silicone composition and method for making. The composition comprises a polysiloxane or silicone resin, at least one linker, and at least one molecular hook.
The present invention relates to topical compositions which provide attachment of functional groups to amino acid based substrates.
As used herein, xe2x80x9ccystine containing, amino acid based substratesxe2x80x9d are proteinaceous materials which contain the amino acid cystine in its amino acid sequence. The phrase xe2x80x9camino acid sequencexe2x80x9d refers to a specific configuration of the amino acids comprising a protein. Cystine amino acid units are represented by Kerxe2x80x94Sxe2x80x94Sxe2x80x94Ker and cysteine amino acid units by Kerxe2x80x94SH. The compositions of the present invention can be used to attach functional groups to materials such as keratin, as found in human and animal hair, skin and nails; various animal body parts such as horns, hooves and feathers; and other naturally occurring protein containing materials, such as wool.
The topical compositions of the present invention can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any of the additional or optional ingredients, components, or limitations described herein.
All percentages, parts and ratios are by weight of the total composition, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the specific ingredient level and, therefore, do not include solvents, carriers, by-products, filler or other minor ingredients that may be included in commercially available materials, unless otherwise specified.
Protected Thiol Compound
The compositions of the present invention comprise a protected thiol compound having the formula
Rxe2x80x94(Sxe2x80x94Pr)m
where R is a mono or multivalent cosmetically active functional group, S is sulfur, Pr is a protecting group, and m is an integer ranging from about 1 to about 100, preferably from about 1 to about 50, more preferably equal to 1 to about 20, and most preferably equal to 1 to about 5.
Typically, the protected thiol compounds of the present invention are present in the compositions of the invention in an amount from about 0.000001% to about 30%, preferably from about 0.0001% to about 25%, more preferably from 0.01 to about 20%, even more preferably from about 0.1% to about 10%, and most preferably from about 1% to about 5%, by weight of the composition. Suitable ranges of amounts will generally depend upon the functional group in question. For example, hair conditioners that are modified with the molecular xe2x80x9chooksxe2x80x9d of the present invention will normally be present from about 0.01% to 10% by weight of the composition, and hair styling agents that are modified such as cationic conditioning polymers or polyisobutylene will normally be present from about 0.01 to 10% by weight of the composition., perfluoropolyether materials that are modified may be present from about 0.000001 to 0.1% by weight of the composition, hair dye chromophoric materials may be present from 0.1% to 10% and other film forming polymers that are modified may be present from about 0.01 to 2% of the composition.
The protected thiol compound comprises from about 1 to about 100, preferably from about 1 to about 50, more preferably from about 1 to 20, and most preferably equal from 1 to about 5 sulfur atoms, each linked to one protective group.
Protecting Group
The protected thiol compounds of the present invention comprise 1 to about 100, preferably 1 to 50, more preferably 1 to 20 and most preferably 1 to 5 protecting groups. The protecting group may be selected from the range consisting of heterocyclic protecting groups, sp2 aliphatic trigonal carbon protecting groups, sp3 carbon protecting groups, metal based protecting groups, non-metal and metalloid based protecting groups, energy-sensitive protecting groups and mixtures thereof. The protecting group is preferably selected from the range consisting of heterocyclic protecting groups, sp2 aliphatic trigonal carbon protecting groups, sp3 carbon protecting groups and non-metal protecting groups. The protecting group is more preferably selected from heterocyclic protecting groups, sp2 aliphatic trigonal carbon protecting groups and non-metal protecting groups.
Heterocyclic Protecting Groupsxe2x80x94The cosmetic composition of the present invention comprises a protected thiol compound wherein the thiol protective group may be a heterocyclic ring or ring system. Heterocyclic groups that are suitable for use in the present invention include mono- or polyunsaturated or saturated heterocyclic rings, heterocyclic ring systems, fused heterocyclic ring systems, substituted heterocyclic rings, substituted heterocyclic ring systems or substituted fused heterocyclic ring systems. The heterocyclic rings contain from about three to about thirty members, and may contain electronegative heteroatoms including N, O, S, or P. The heterocyclic rings or ring systems also may contain exocyclic double bonds of the Cxe2x95x90M type wherein M is O, S, NA1 or CA1A2. A1 and A2 used here, and A3 and A4 used hereinafter, each represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or polycyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0xe2x80x9415 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or perfluoro substitution.
Optional substituents on the heterocyclic ring or ring system, X1, X2, X3, X4, X5 . . . , can be selected from electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between xe2x88x921.0 and +1.5 which can be non-ionic, zwitterionic, cationic or anionic comprising for example C-linked groups of the classes defined above as A1, A2, A3, and A4; S-linked groups including SA1, SCN, SO2A1, SO3A1, SSA1, SOA1, SO2NA1A2, SNA1A2, S(NA1)A2, S(O)(NA1)A2, SA1(NA2), SONA1A2; O-linked groups including OA1, OOA1, OCN, ONA1A2; N-linked groups including NA1A2, NA1A2A3+, NC, NA1OA2, NA1SA2, NCO, NCS, NO2, Nxe2x95x90NA1, Nxe2x95x90NOA1, NA1CN, Nxe2x95x90Cxe2x95x90NA1, NA1NA2A3, NA1NA2NA3A4, NA1Nxe2x95x90NA2; other miscellaneous groups including COHal, CON3, CONA12, CONA1COA2, C(xe2x95x90NA1)NA1A2, CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of X1, X2, X3, X4, X5 via a ring system;
Ak is A1, A2, A3, and A4 or X1, X2, X3, X4 , X5 . . .
Hal is F, Cl, Br, or I.
H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluorine, R is any cosmetically active, functional group or benefit agent as described herein below.
The invention includes the following preferred non-limiting heterocyclic exemplary classes and their X1, X2, X3, X4, X5 . . . substituted derivatives [Herein referred to as Class I]:
Six membered heterocycles with a single heteroatom such as pyridine: 
Six membered heterocycles with two heteroatoms such as pyrimidines, pyrazines and pyridazines: 
Six membered heterocycles with three and four heteroatoms such as triazines and tetrazines: 
Six membered O, N, and/or S containing heterocycles with Cxe2x95x90O, Cxe2x95x90S or Cxe2x95x90C exocyclic groups: 
Cationic six membered heterocycles with one heteroatom such as pyridinium, pyrylium, and thiopyrylium salt derivatives: 
Cationic six membered heterocyclics with two heteroatoms such as pyrimidinium and pyrazinium salt derivatives: 
Five membered heterocycles with one heteroatom such as furans, pyrroles, and thiophenes: 
Five membered heterocycles with two heteroatoms such as pyrazoles, isoxazoles, and isothiazoles: 
Five membered heterocyclics with three heteroatoms such as 1,2,4-triazoles, 1,2,3-triazoles, 1,2,4-oxadiazoles, and 1,2,4-thiadiazoles: 
Five membered cationic heterocycles with two or more heteroatoms such as pyrazolium and triazolium: 
Seven membered heterocycles such as azepines, oxepins and thiepins: 
Seven membered cationic heterocycles such as thiepinium salts: 
and related variations including combinations of the above heterocycles in a ring system and fused systems both of which may include carbocyclic rings without heteroatoms. The cationic heterocycles will also incorporate a Clxe2x88x92, Brxe2x88x92, Ixe2x88x92 or other suitable negatively charged counterion.
The invention may also include heterocyclic compounds comprising the cosmetic active, R, that are capable of generating a thiol via a ring-opening mechanism. Such compounds are represented by the following structures: 
wherein at least one cosmetic group, R, comprises or is attached to any of the X1, X2, X3 groups.
Q1 and Q2 represent, independently from one another, a divalent group comparable to A1 but with the open valencies separated by 0 to 4 atoms.
W1 represents an electron withdrawing group with a Hammett sigma para value more positive than 0.10 comprising C-linked groups of the classes defined above as A1, A2, A3; S-linked groups including SA1, SCN, SO2A1, SO3A1, SSA1, SOA1, SONA1A2, SO2NA1A2, SNA1A2, S(NA1)A2, S(O)(NA1)A2, SA1(NA2); O-linked groups including OA1, OOA1, OCN, ONA1A2; N-linked groups including NA1A2, NA1A2A3+, NC, NA1OA2, NA1SA2, NCO, NCS, NO2, Nxe2x95x90NA1, Nxe2x95x90NOA1, NA1CN, Nxe2x95x90Cxe2x95x90NA1, NA1NA2A3, NA1NA2NA3A4, NA1Nxe2x95x90NA2; other miscellaneous groups including COHal, CON3, CONA12, CONA1COA2, C(xe2x95x90NA1)NA1A2, CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of X1, X2, X3, X4, X5 via a ring system;
L1 is a suitable leaving group including but not limited to SA1, OA1, or NA1A2.
Below are some non-limiting representative examples for each of the above heterocyclic structures (II through XV) that are capable of generating a thiol via a ring-opening mechanism:
A thiolactone, thiophthalide, and thiazolidinone (classes II, III and IV), 
A dihydrothiophene, dihydrothiopyran, and dihydro-1,4-thiazine (classes V, VI and VII), 
Unsaturated thiolactones and a dihydrothiapyrone (classes VIII, IX and X), 
A dihydrothiepin, thiopyran and thiepinone (classes XI, XII and XIII), 
A dihydrothiazoline and 2-methoxythiazolidine (classes XIV and XV), 
and other related derivatives.
Preferred protected thiol compounds of the heterocyclic thiol protective type include the following non-limiting examples: 
and mixtures thereof, wherein Hal is Clxe2x88x92, Brxe2x88x92, Ixe2x88x92 or any suitable negatively charged counterion.
sp2 Aliphatic Trigonal Carbon Protecting Groupsxe2x80x94The protecting groups of the present invention may comprise a sp2 carbon moiety wherein the divalent sulfur atom is bonded on one side to the cosmetic active and on the other side to a sp2 carbon atom. Protecting groups of the sp2 aliphatic trigonal carbon type that are suitable for the present invention include (a) aliphatic trigonal carbon atoms double bonded to O, S, N, or C, 
which includes derivatives of the following acids: thiocarboxylic (Rxe2x80x94Sxe2x80x94C(O)CH2xe2x80x94A1), carbonodithioic (Rxe2x80x94Sxe2x80x94C(O)Sxe2x80x94A1, Rxe2x80x94Sxe2x80x94C(S)Oxe2x80x94A1), carbonothioic (Rxe2x80x94Sxe2x80x94C(O)Oxe2x80x94A1), carbamothioic (Rxe2x80x94Sxe2x80x94C(O)Nxe2x80x94A1A2), dithiocarboxylic (Rxe2x80x94Sxe2x80x94C(S)CH2xe2x80x94A1), carbonotrithioic (Rxe2x80x94Sxe2x80x94C(S)Sxe2x80x94A1), carbamodithioic (Rxe2x80x94Sxe2x80x94C(S)Nxe2x80x94A1A2), carboximidothioic (Rxe2x80x94Sxe2x80x94C(NA1)CH2xe2x80x94A1), carbonimidodithioic (Rxe2x80x94Sxe2x80x94C(NA1)Sxe2x80x94A1), and carbonimidothioic (Rxe2x80x94Sxe2x80x94C(NA1)Oxe2x80x94A1) acids. Suitable sp2 aliphatic trigonal carbon type protecting groups for use in the topical compositions of the present invention do not include carbamimidothioic acids.
The invention also includes (b) related sp2 carbon derivatives that are capable of releasing a cosmetic thiol via an intramolecular nucleophilic attack and release mechanism, 
(c) sp2 carbon derivatives that are capable of rearranging to produce a cosmetic containing thiol via an intramolecular nucleophilic attack and rearrangement mechanism, 
as well as (d) trigonal carbon electrophiles of the anhydride, thioanhydride, and secondary/tertiary amide type, 
and related aliphatic trigonal carbon variations. The cationic protecting groups will also incorporate a Clxe2x88x92, Brxe2x88x92, Ixe2x88x92 or other suitable negatively charged counterion.
M1, M2 are O, S, NA1, NOA1, NA1A2+, CA1xe2x95x90CA2Y1, SA+, OA+.
E1 is O, S, NA1, CA1A2.
Nu is NHA1A2+, NA1A2, OHA1+, OA1.
X1 represents an electron withdrawing or electron donating group with a Hammett sigma para value between xe2x88x921.0 and +1.5 which can be non-ionic, zwitterionic, cationic or anionic comprising for example C-linked groups of the classes defined below as A1, A2, A3; S-linked groups including SA1, SCN, SO2A1, SO3A1, SSA1, SOA1, SONA1A2, SO2NA1A2, SNA1A2, S(NA1)A2, S(O)(NA1)A2, SA1(NA2); O-linked groups including OA1, OOA1, OCN, ONA1A2; N-linked groups including NA1A2, NA1A2A3+, NC, NA1OA2, NA1SA2, NCO, NCS, NO2, Nxe2x95x90NA1, Nxe2x95x90NOA1, NA1CN, Nxe2x95x90Cxe2x95x90NA1, NA1NA2A3, NA1NA2NA3A4, NA1Nxe2x95x90NA2; other miscellaneous groups including COHal, CON3, CONA12, CONA1COA2, C(xe2x95x90NA1)NA1A2, CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of X1, X2, X3, X4, X5 via a ring system; A1, A2 represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly-cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or per fluoro substitution.
Q is a divalent group comparable to A1 but with the open valencies separated by 2 to 7 atoms.
Hal is F, Cl, Br, or I.
Y1 represents electron an withdrawing substituent with a Hammett sigma para value more positive than 0.10. Such electron withdrawing substituents which can be nonionic, zwitterionic, cationic or anionic include the following non-limiting examples: NO2, CN, COOA1, CONA1A2, C(O)A1, SO2A1, SO2OA1, NO, COHal, CON3, CONA1A2, CONA1COA2, C(xe2x95x90NA1)NA2A3, C(S)A1, NC, SCN, SO2A1, SO3A1, SOA1, SO2NA1A2, SNA1A2, S(NA1)A2, S(O)(NA1)A2, NA1A2A3+, SA1A2+.
H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluorine, R is any cosmetically active functional group or benefit agent as described herein below.
Non-limiting examples of suitable X1 groups are as follows: 
or related derivatives.
Preferred protected thiol compounds of the carbon thiol protective type include the following non-limiting examples: 
sp3 Carbon Protecting Groups The protecting groups of the present invention may comprise an sp3 carbon moiety wherein the divalent sulfur atom is bonded on one side to the cosmetic active and on the other side to a sp3 carbon atom. Protecting groups of the sp3 carbon type that are suitable for the present invention include those of the thioether type, 
including the monothioacetal (II. X1=H), monothioketal (II. X1, X2=H), monothioortho ester (III) and monothioorthocarbonate (IV) type, 
the dithioacetal(V. X1=H), dithioketal (V. X1, X2=H), dithioorthoester (VI) and dithioorthocarbonate (VII) type, 
the trithioorthoester type (VIII), 
the thiohemiaminal (IX), monothioorthoamide (X) and dithioorthoamide (XI) type, 
and related classes wherein X1, X2, X3 represent, independently from one another, electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between xe2x88x921.0 and +1.5 which can be non-ionic, zwitterionic, cationic or anionic comprising for example C-linked groups of the classes defined below as A1, A2, A3; S-linked groups including SA1, SCN, SO2A1, SO3A1, SSA1, SOA1, SONA1A2, SO2NA1A2, SNA1A2, S(NA1)A2, S(O)(NA1)A2, SA1(NA2); O-linked groups including OA1, OOA1, OCN, ONA1A2; N-linked groups including NA1A2, NA1A2A3+, NC, NA1OA2, NA1SA2, NCO, NCS, NO2, Nxe2x95x90NA1, Nxe2x95x90NOA1, NA1CN, Nxe2x95x90Cxe2x95x90NA1, NA1NA2A3, NA1NA2NA3A4, NA1Nxe2x95x90NA2; other miscellaneous groups including COHal, CON3, CONA12, CONA1COA2, C(xe2x95x90NA1)NA1A2, CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of X1, X2, X3, X4, X5 via a ring system. Hal is F, Cl, Br, or I.
For the thioether class, as defined above, at least one of X1, X2, or X3 groups is electron donating such that the sum of the Hammett sigma para values for X1, X2, X3 is negative for this class.
A1, A2, A3, A4 represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly-cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or per fluoro substitution.
H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluorine, R is any cosmetic active, functional group or benefit agent as described herein below.
Preferred electron donating substituents for X1, X2, X3 are aromatic or heteroaromatic derivatives which include the following non-limiting examples: 
plus other related derivatives.
Preferred protected thiol compounds chosen from classes I through XI above include the following non-limiting examples: 
The present invention also includes organosulfur molecular xe2x80x9chooksxe2x80x9d wherein the potential cosmetic thiol is bonded directly to an sp3 carbon atom that is part of a group capable of undergoing heterolytic xcex2-elimination, the reversal of Michael Addition reactions, to liberate a thiol, Suitable sp3 carbon groups capable of undergoing heterolytic xcex2-elimination are represented in the compounds, 
wherein Y1 and Y2 represent, independently from one another, electron withdrawing substituents with a combined Hammett sigma para value more positive than 0.10. Such electron withdrawing substituents include the following non-limiting examples: NO2, CN, COOA1, CONA1A2, C(O)A1, SO2A1, SO2OA1, NO, COHal, CON3, CONA1A2, CONA1COA2, C(xe2x95x90NA1)NA2A3, C(S)A1, NC, SCN, SO2A1, SO3A1, SOA1, SONA1A2, SO2NA1A2, SNA1A2, S(NA1)A2, S(O)(NA1)A2, NA1A2A3+, SA1A2+ and aromatic and heteroaromatic derivatives.
Some non-limiting examples of aromatic and heteroaromatic electron withdrawing groups for Y1 and Y2 include the following: 
plus other related derivatives.
Preferred hook compounds that are capable of undergoing heterolytic xcex2-elimination, the reversal of Michael Addition reactions, to liberate a thiol include the following non-limiting examples: 
The present invention also includes cases wherein the cosmetic thiol is protected by being bonded directly to an sp3 carbon atom that is incorporated within a ring structure. Suitable sp3 carbon ring systems are represented by the following, 
wherein Z is O, NAk, S, (CH2)0-2 or 
L1 is A1 or part of a 5 to 7 membered fused ring system. The above ring system(s) can carry any substituents. Specific examples of sp3 carbon ring compounds covered by the present invention include the following non-limiting examples: 
and other related derivatives.
A1, A2, A3, represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly-cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or per fluoro substitution.
H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluorine, R is any cosmetically active functional group or benefit agent as described herein be low.
Metal Based Protecting Groupsxe2x80x94The molecular xe2x80x9chooksxe2x80x9d of the present invention comprise a divalent sulfur atom that is bonded on one side to the cosmetic active and on the other side to an alkaline earth metal, transition metal or a representative metal in groups IIA, IIIA, IVA, VA, VIA, VIIA, VIII, IB, IIB, IIIB, IVB, VB, VIB, and VIIB of the periodic table of the elements including Mg, Ca, Sr, Ba, La, Ti, Zr, V, Cr, Mo, W, Mn, Fe, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, In, Sn, and Bi. Protected thiol compounds comprising such heavy metal mercaptides are represented by the following: 
wherein Met is an alkaline earth metal, transition metal or a representative metal in groups IIA, IIIA, IVA, VA, VIA, VIIA, VIII, IB, IIB, IIIB, IVB, VB, VIB, and VIIB of the periodic table of the elements including Mg, Ca, Sr, Ba, La, Ti, Zr, V, Cr, Mo, W, Mn, Fe, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, In, Sn, and Bi. Also, wherein n and m are zero or integers such that 1+2 m+n equals the valency of Met.
X represents independent electron withdrawing, electron neutral or electron donating groups with Hammett sigma para values between xe2x88x921.0 and +1.5 which can be non-ionic, zwitterionic, cationic or anionic comprising for example C-linked groups of the classes defined below as A1, A2, A3; S-linked groups including SA1, SCN, SO2A1, SO3A1, SSA1, SOA1, SONA1A2, SO2NA1A2, SNA1A2 S(NA1)A2, S(O)(NA1)A2, SA1(NA2); O-linked groups including OA1, OOA1, OCN, ONA1A2; N-linked groups including NA1A2, NA1A2A3+, NC, NA1OA2, NA1SA2, NCO, NCS, NO2, Nxe2x95x90NA1, Nxe2x95x90NOA1, NA1CN, Nxe2x95x90Cxe2x95x90NA1, NA1NA2A3, NA1NA2NA3A4, NA1Nxe2x95x90NA2; other miscellaneous groups including COHal, CON3, CONA12, CONA1COA2, C(xe2x95x90NA1)NA1A2, CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of X1, X2, X3, X4, X5 via a ring system. Hal is F, Cl, Br, or I.
A1, A2, A3, A4 represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly- cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or per fluoro substitution.
M is a divalent group such as O, S, NA1 or CA1A2.
H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluorine, B is boron, Al is aluminum, Si is silicon, N is nitrogen, Mg is magnesium, Ca is calcium, Sr is strontium, Ba is barium, La is lanthanum, Ti is titanium, Zr is zirconium, V is vanadium, Cr is chromium, Mo is molybdenum, W is tungsten, Mn is manganese, Fe is iron, Co is cobalt, Rh is rhodium, Ni is nickel, Pd is palladium, Pt is platinum, Cu is copper, Ag is silver, Au is gold, Zn is zinc, In is indium, Sn is tin, Bi is bismuth, and R is any cosmetic active, functional group or benefit agent as described herein below.
Also wherein at least one substituent, X, or the cosmetic active, R, contains salt forming or water solubilizing groups including, but not limited to, COOxe2x88x92, SO3xe2x88x92, NH3+, OH, COOA1, (CH2CH2O)nA1, CONA1A2, OSO3+, OPO3Hxe2x88x92, NA1A2A3+, and the like.
Preferred metal based protecting groups of the present invention include, but are not limited to, the following examples, 
Non-metal and metalloid based Protecting Groupsxe2x80x94The molecular xe2x80x9chooksxe2x80x9d of the present invention comprise a divalent sulfur atom that is bonded on one side to the cosmetic active and on the other side to a representative non-metal or metalloid atom including boron, aluminum, silicon, germanium, nitrogen, phosphorus, sulfur, selenium, antimony, and tellurium. Molecular xe2x80x9chooksxe2x80x9d whereby a divalent sulfur atom of a potential cosmetic thiol is bonded directly to these representative non-metals and metalloids are represented by the following: 
wherein E is a representative non-metal or metalloid element including B, Al, Si, Ge, N, P, S, Se, Sb, and Te. Also, wherein n and m are zero or integers such that 1+2 m+n equals the valency of E.
X represents independent electron withdrawing, electron neutral or electron donating groups with Hammett sigma para values between xe2x88x921.0 and +1.5 which can be non-ionic, zwitterionic, cationic or anionic comprising for example C-linked groups of the classes defined below as A1, A2, A3; S-linked groups including SA1, SCN, SO2A1, SO3A1, SSA1, SOA1, SONA1A2, SO2NA1A2, SNA1A2, S(NA1)A2, S(O)(NA1)A2, SA1(NA2); O-linked groups including OA1, OOA1, OCN, ONA1A2; N-linked groups including NA1A2, NA1A2A3+, NC, NA1OA2, NA1SA2, NCO, NCS, NO2, Nxe2x95x90NA1, Nxe2x95x90NOA1, NA1CN, Nxe2x95x90Cxe2x95x90NA1, NA1NA2A3, NA1NA2NA3A4, NA1Nxe2x95x90NA2; other miscellaneous groups including COHal, CON3, CONA12, CONA1COA1, C(xe2x95x90NA1)NA1A2, CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of X1, X2, X3, X4, X5 via a ring system. Hal is F, Cl, Br, or I.
M is a divalent group such as O, S, NA1 or CA1A2.
A1, A2, A3, A4 represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly-cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or per fluoro substitution.
H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluorine, B is boron, Al is aluminum, Si is silicon, Ge is germanium, N is nitrogen, P is phosphorus, Te is tellurium, and R is any cosmetic active, functional group or benefit agent as described herein below.
Preferred thiol protective systems utilizing non-metals and metalloids of the present invention include, but are not limited to, the following examples, 
Energy-sensitive Protecting Groupsxe2x80x94The topical compositions of the present invention may also comprise a protected thiol compound wherein the protecting group is energy-sensitive. Protected thiol compounds comprising energy-sensitive protecting groups are chemically stable in solution. Such potential thiols are protected until a suitable source of energy is applied to the composition. Upon application of a suitable energy source, the energy-sensitive protecting groups become labile, thereby releasing the reactive thiol. Typically, the energy source will be light. Once the thiols are released, they are capable of reacting with amino acid residues present in keratinaceous substrates to enable durable cosmetic benefits.
As mentioned above, the protected thiols are activated by applying a suitable energy source to the composition, i.e., irradiation, which converts the photoactivatable protected thiol compounds to fully reactive thiol compounds. The byproducts of the energy activation of the protecting group will usually be removed from the substrate by washing.
Many different energy-sensitive groups can be employed for protecting thiols used in the topical compositions of the present invention. Typically, the thiol groups are protected with a photoactivatable protecting group that is capable of liberating or releasing the reactive thiol by irradiation. The properties and uses of photoreactive compounds have been reviewed. See McCray et al, 1989, Ann. Rev. Biophys. Chem. 18:239-270, which is incorporated herein by reference. The photosensitive groups will preferably be activatable by low energy ultraviolet or visible light. Many, although not all, of the energy-sensitive protecting groups are aromatic compounds. Suitable photoremovable protecting groups are also described in, for example, Patchornik, 1970, J. Am. Chem. Soc. 92:6333, and Amit et al, 1974, J. Org. Chem. 39:192, which are incorporated herein by reference. More preferably, the energy-sensitive protecting group will be a nitrobenzylic compound, such as o-nitrobenzyl or benzylsulfonyl groups. Suitable examples include 6-nitroveratryloxycarbonyl (NVOC); 6-nitropiperonyloxycarbonyl (NPOC); alpha, alpha-dimethyldimethoxybenzyloxycarbonyl (DDZ), methyl 6-nitroveratryloxycarbonyl (MenVOC), methyl-6-nitropiperonyloxycarbonyl (MeNPOC), or 1-pyrenylmethyl. The energy-sensitive protecting group may also be of the silyl type as described in Pirrung and Lee, 1993, J. Org. Chem. 58:6961-6963 and Pirrung and U.S. Pat. No. 5,486,633, issued to Lee, both incorporated by reference herein. Suitable examples include (hydroxystyryl)dimethylsilyl (HSDMS) and (hydroxystyryl)diisopropylsilyl (HSDIS).
Clearly, many energy-sensitive protecting groups are suitable for use in the present method. Some examples of acceptable energy-sensitive protecting groups are presented in Table 1, below, together with their corresponding wavelengths for deprotection.
The composition containing the cosmetic active protected with the energy-sensitive group may be activated with energy both prior or during usage. For instance, the energy source may be applied to the composition for a sufficient time period to activate the energy sensitive protecting group either before, during or after the composition is applied to the substrate. The energy source may include various types of electromagnetic radiation including ultraviolet, visible, near infrared, infrared, far infrared or microwave. In a preferred embodiment, the radiation is UV, near IR or visible light.
Examples of suitable protecting groups that are capable of undergoing photochemical or thermal thiol deprotection include, but are not limited to, the following: 
Examples: 
Examples: 
Examples: 
Example: 
Example: 
Examples: 
X1, X2, X3, X4 and X5 can be selected from electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between xe2x88x921.0 and +1.5 which can be non-ionic, zwitterionic, cationic or anionic comprising for example C-linked groups of the classes defined below as A1, A2, A3; S-linked groups including SA1, SCN, SO2A1, SO3A1, SSA1, SOA1, SONA1A2, SO2NA1A2, SNA1A2, S(NA1)A2, S(O)(NA1)A2, SA1(NA2); O-linked groups including OA1, OOA1, OCN, ONA1A2; N-linked groups including NA1A2, NA1A2A3+, NC, NA1OA2, NA1SA2, NCO, NCS, NO2, Nxe2x95x90NA1, Nxe2x95x90NOA1, NA1CN, Nxe2x95x90Cxe2x95x90NA1, NA1NA2A3, NA1NA2NA3A4, NA1Nxe2x95x90NA2; other miscellaneous groups including COHal, CON3, CONA21, CONA1COA2, C(xe2x95x90NA1)NA1A2, CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of X1, X2, X3, X4, X5 via a ring system;
A1, A2 represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly-cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or per fluoro substitution.
Mono or Multivalent Cosmetically Active Functional Group
The mono or multivalent cosmetically active functional, R, suitable for inclusion in the present invention may be any compound that imparts one or more visual, tactile or other cosmetic beneficial effects on proteinaceous materials such as keratin, i.e., hair, animal fur or wool. Any cosmetic compound may be included as a functional group in the compositions of the present invention as long as the compound can be modified to contain at least one divalent sulfur atom linked to a suitable protecting group as described herein.
Suitable functional groups that can be protected as thiol derivatives include but are not limited to antimicrobial compounds, UV-absorbing compounds, skin conditioning agents, hair conditioning agents, hair repair agents, hair styling agents, hair dyes, scalp treatment agents, anti-inflammatory compounds, antioxidants, dyes and coloring agents, perfumes, oral care actives, skin moisturizers, pharmaceutical agents, antidandruff agents, insect repellents, moisturizers, humectants, pearlescent and/or opacifying materials, fabric care actives, pet grooming actives, fabric anti-wrinkling agents, shrink-resistant actives, laundry care actives, hard surfaces actives, textile actives, textile dyes, water-proofing agents, cationic polymers, cationic surface modifiers, hydrophobic surface modifiers, anionic surface modifiers, absorbents, antifungal agents, insecticidal agents, textile color guards, nail actives such as enamel and polish, eyelash actives and mascara, antiperspirant and deodorant actives, anti-acne actives, odor control actives, fluorescent actives, bleaching agents, enzymes, antibodies, dispersing aids, emollients, stabilizers, anti-static agents, anti-seborrhea agents, optical brighteners, fluorescent dyes, softeners, cross-linking agents, photobleaches, bactericides, and mixtures thereof.
Examples of suitable antimicrobials which can be protected as thiol derivatives include but are not limited to derivatives of phenol, cresol, hydroxybenzoates, Triclosan(copyright), Tricarban(copyright), chlorhexidine, metal salts (e.g. zinc citrate, sodium zinc citrate, zinc pyridinethione, and stannous pyrophosphate) sanguinarine extract, metronidazole, quaternary ammonium compounds (chlorhexidine digluconate, hexetidione, octenidine, alexidine), halogenated bisphenolic compounds such as 2,2xe2x80x2-methylenebis-(4-chloro-6-bromophenol), and salicylanilide.
Examples of suitable UV-absorbing materials which can be protected as thiol derivatives include but are not limited to derivatives of benzoates, oxybenzones, cinnamic acid, PARSOL MCX esters, benzotriazoles, and benzophenones.
Examples of suitable skin conditioners or moisturizers which can be protected as thiol derivatives, include but are not limited to derivatives of alpha-hydroxy acids, polyols, hyaluronic acid, petrolatum, vegetable oils, esters of fatty acids, and mineral oil. Such skin conditioners or moisturizers are bound to the velus hairs present on the skin, and not the skin directly, to achieve the long lasting skin benefits.
Examples of suitable anti-inflammatory agents which can be protected as thiol derivatives include but are not limited to corticosteroids or salicylates.
Examples of suitable antioxidants which can be protected as thiol derivatives include but are not limited to ascorbates and gallates.
Examples of suitable hair conditioners which can be protected as thiol derivatives include but are not limited to intact or modified proteins, such as hydrolyzed keratin, collagen, elastin, hemoglobin, silk, rice, soy, wheat protein, corn, fibronectin, reticulum, serum protein, wheat gluten, peptides and peptide derivatives; amino acids; hydroxylated fats; glycinates; silicone polymers, such as siloxane gums and resins, volatile or non-volatile silicone oils, amino- (or other) functional silicones, and other silicone-containing polymers; hydrocarbon based conditioners including C8-C30 alkyl, alkenyl, modified alkyl or modified alkenyl, branched alkyl and branched alkenyl groups as well as long chain alkyl groups that are ethoxylated or substituted with various non-ionic, cationic or anionic functional groups including quats, amines, amides, esters, hydroxyls, carboxylates, and the like; polysaccharides or monosaccharides, and alkyl cationic conditioning polymers such as cationic derivatives of guar gum and cellulose ether derivatives; poly(ethyleneoxides) and alkyl capped poly(ethyleneoxides) of molecular weights ranging from 100 to 10,000,000; and herb or other plant extracts, essential oils etc.
Examples of suitable hair styling agents which can be protected as thiol derivatives include but are not limited to film-forming polymers such as polyvinylpyrrolidone/vinyl acetate copolymer; styling copolymers comprising silicone macromonomers, U.S. Pat. Nos. 5,618,524 and 5,658,557, cationic polymers, such as those disclosed in GB-A-2161172 (Beecham), GB-A-2122214 (Unilever) and GB-A-2050166 (L""Oreal); and hydrocarbon polymers, such as polyisobutylene; perfluoro-aliphatic and perfluoro-aromatic compounds.
Examples of suitable dyes and coloring agents which can be protected as thiol derivatives include but are not limited to phenol, naphthols, acid dyes, azo derivatives; vegetable dyes, metallized dyes, nitrobenzene dyes, quinone-imine dyes, basic dyes, quaternary dyes, and oxidation dyes.
Examples of suitable fragrances that can be protected as thiol derivatives include but are not limited to phenols such as menthyl salicylate, thymol, and vanillin.
Examples of suitable cationic polymers that can be protected as thiol derivatives include but are not limited to derivatives of quaternary ammonium salts of hydroxyethylcellulose, cationic copolymers of acrylic acid and acrylamide, cationic guar polymers, copolymers of vinylimidazolium methochloride and vinylpyrrolidone, polyethylenimines, and other cationic polymers and resins known to those skilled in the art.
Examples of suitable oral care active agents that can be protected as thiol derivatives include but are not limited to anti-caries agents such as amine fluorides, monosodium fluorophosphate, casein; plaque buffers such as urea, calcium lactate, calcium glycerophosphate; anti-plaque agents; agents for alleviating sensitive teeth, e.g. potassium and strontium salts, particularly those of carboxylic acids; materials that form films and block pores; oral pharmaceutical actives, (e.g. ibuprofen, flurbiprofen, aspirin and indomethacin); biomolecules such as peptides, antibodies and enzymes; anti-tartar agents; agents for treating bad breath such as zinc salts; and anti-calculus agents (e.g. alkali metal pyrophosphates, hypophosphite-containing polymers, organic phosphonates, and phosphocitrates).
Examples of suitable pharmaceutical agents that can be protected as thiol derivatives include but are not limited to medicinal agents, metabolic agents and other therapeutic agents of benefit in treating the human body.
Examples of antidandruff agents that can be protected as thiol derivatives include but are not limited to zinc pyridinethione, Octopirox(copyright), climbazole and itroconazole.
An example of odor control actives that can be protected as thiol derivatives include the class of cyclodextrins. In addition to trapping odors on the substrate, the cyclodextrins can plausibly be utilized to deliver cosmetic actives molecules to the substrate such as perfumes that can be liberated slowly.
Other non-limiting classes of beneficial cosmetic actives include sealants, binders, resins, adhesives, waxes, drying oils, varnishes, and latex finishes which comprise urethanes, polysulfides, acrylics, butyl polymers, maleated oils, cellulosics, starches etc.
The mono or multivalent cosmetically active functional preferably used in the present compositions is dependent on the product form desired. Hair care compositions preferably use hair conditioners, hair styling agents, dyes and coloring agents, sunscreens, fragrances, antidandruff agents, or mixtures thereof as the functional group. Preferable functional groups in textile care compositions include dyes and coloring agents, odor control actives, sealants, fragrances, and mixtures thereof. Cosmetic compositions preferably comprise dyes and coloring agents, sealants, resins, varnishes, latex finishes, and mixtures thereof. Oral care compositions preferably comprise anti-caries agents, plaque buffers, anti-plaque agents, agents for alleviating sensitive teeth, materials that form films and block pores, oral pharmaceutical actives, biomolecules, anti-tartar agents, agents for treating bad breath, anti-calculus agents, and mixtures thereof as functional groups. Pharmaceutical composition preferably select mono or multivalent cosmetically active functional groups from the group consisting of medicinal agents, metabolic agents, therapeutic agents, anti-inflammatory compounds, and mixtures thereof. Animal care composition preferably comprise antimicrobial agents, insect repellents, grooming actives, and mixtures thereof as functional groups.
Optional Activating Mechanisms
As explained above, the molecular xe2x80x98hooksxe2x80x99 of the present invention may be activated via a number of mechanisms either before, during or after the application of the topical compositions containing the protected thiol to the substrate. Various embodiments of the present invention are systems which comprise both the topical composition herein with an activating mechanism.
Such activation could be achieved via hydrolysis by the use of a mechanism to manipulate the pH of the environment surrounding the compound. Such pH adjusting mechanisms may include acidic or alkaline solutions. Whether acidic or alkaline mechanisms are required is dependent on the protecting group used. Hydrolysis may also be achieved via simply mixing the compound, delivered in its purified form or from a non-aqueous solution, with water.
Furthermore, the molecular xe2x80x98hookxe2x80x99 could be activated by coming in contact with a suitable nucleophile. Such nucleophiles include, but are not limited to, nitrogen-containing functional groups, for example amines, oxygen-containing functional groups, for example hydroxyl groups, phosphorus-containing functional groups, for example phosphines, and sulfur-containing functional groups, for example thiol groups and sulfites. For instance, the solution containing the xe2x80x98hookxe2x80x99 compound could be inter-mixed with a separate solution containing a nucleophile including reducing agents such as ammonium thioglycolate or sodium bisulfite, either before, during or after application of the compound to the substrate.
Conversely, the xe2x80x98hookxe2x80x99 compound could be activated by nucleophilic groups present in the substrate itself as in the case of hair that has been reduced or cold waved, i.e. hair that has been treated with a reducing agent either prior to or simultaneous to the application of the xe2x80x98hookxe2x80x99 compound. The resulting activated thiol xe2x80x98hookxe2x80x99 could then react directly as a nucleophile with keratinaceous disulfides or oxidatively with the nucleophilic groups present in the substrate, e.g. with free thiol groups that were formed during cold waving or reduction. Of course, the latter process could be accelerated or enhanced via the addition of oxidation reagents, i.e. peroxide as in the neutralization step of cold waving of hair.
The activation could also be accented via heat or a suitable energy source. For instance, the energy source could be applied to the composition for a sufficient time period to activate the protecting group either before, during or after the composition is applied to the substrate. The energy source may include various types of electromagnetic radiation including ultraviolet, visible, near infrared, infrared, far infrared or microwave radiation.
Other various adjuncts that could possibly influence the activation and/or the performance of the xe2x80x9chookxe2x80x9d compounds of the present invention include, but are not limited to, (i) Lewis acids such as zinc acetate, tin chloride, zinc chloride, zinc stearate, titanium ethoxide, and aluminum tosylate, metal salts such as zinc sulfate, and magnesium sulfate, (ii) chelators such as tetrasodium EDTA, disodium EDTA, (iii) ionic species capable of ion-pairing including anions, cations, quats, amphoterics zwitterions etc, (iv) dispersing aids such as anionic surfactants, non-ionic surfactants, anionic surfactants, amphoteric surfactants, and zwitterionic surfactants, (v) keratin swelling aids such as ammonia, amines, urea, phosphoric acid, acetic acid and other swelling aids known to those skilled in the art, and (vi) solvent systems wherein the individual solvent molecules are nucleophiles themselves as defined above.
Another embodiment of the present invention comprises a kit comprising the system comprising the topical compositions of the present invention and either a pH manipulating mechanism or a nucleophile mechanism, and a package comprising a first and second chamber; wherein the topical composition is packaged in and delivered out of one chamber and the activation mechanism is packaged in and delivered out of the second chamber.
Other Optional Ingredients
The topical composition according to the invention can also typically include an acceptable vehicle to act as a dilutant, dispersant, or carrier for the protected thiol compounds in the composition, so as to facilitate the distribution of the protected thiol compounds when the composition is applied to the keratinaceous substrate, i.e., hair, nails, wool, skin etc.
Vehicles other than water can include liquid or solid emollients, solvents, humectants, thickeners and powders. Examples of each of these types of vehicle, which can be used singly or as a mixture of one or more vehicles, are as follows:
Emollients, such as stearyl alcohol, glyceryl monoricinoleate, glyceryl monostearate, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isododecane, isocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as polydimethylsiloxane, cyclomethicone, di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, dimethyl malonate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cotton seed oil, tallow lard, olive oil, palm kernel oil, rapeseed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, olive oil, sesame seed oil, coconut oil, arachis oil, castor oil, acetylated lanolin alcohols, petroleum jelly, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate.
Propellants, such as trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethane, monochlorodifluoromethane, trichlorotrifluoroethane, propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide;
Solvents includc, but are not limited to, ethyl alcohol, n-propanol, n-butanol, tert-butanol, ethylene glycol dimethyl ether, hexane, tetramethylurea, sulfolane, low molecular weight poly(ethylene oxide), glycerol, propylene glycol, 2-butoxyethanol, amyl alcohol, n-octanol, n-decanol, acetone, acetic acid, butyl acetate, methylene chloride, isopropanol, acetone, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulphoxide, dimethylformamide, tetrahydrofuran;
Powders, such as chalk, talc, fullers earth, kaolin, starch, gums, colloidal silica, sodium polyacrylate, tetraalkyl- and/or trialkyl-arylammonium smectites, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, aluminum silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethylcellulose, ethylene glycol monostearate.
The cosmetically acceptable vehicle will usually form from 10 to 99.9%, preferably from 50 to 99% by weight of the composition and can, in the absence of other cosmetic adjuncts, form the balance of the composition.
The topical compositions according to the invention may be provided in any suitable physical form, for example as low to moderate viscosity liquids, lotions, milks, mousses, dispersions, sprays, gels, foams, aerosols, and creams. These compositions may be produced by procedures well known to the skilled artisan. The cosmetic compositions can be used in various manners as other known compositions in the art including but not limited to various rinse-off and leave-on applications such as hair shampoos, skin cleansers, skin lotions, hair conditioners, styling sprays, hair mousses, two-in-one shampoos, fabric softeners, lotions, nail polishes, hair serums, hair dyes, hair waving, etc. The contact time between the cosmetic composition of the present invention and the substrate varies between 10 seconds and about 1 hour, preferably between 20 seconds and 30 minutes, more preferably between 30 seconds and 15 minutes.
The cosmetic composition of the present invention can be formulated as a fluid, lotion, fluid cream or cream having a viscosity from 500 to 100,000 mPas or above. The composition can be packaged in a suitable container to suit its viscosity and intended use by the consumer. For example, a lotion or fluid cream can be packaged in a bottle or a roll-ball applicator or a propellant-driven aerosol device or a container fitted with a pump suitable for hand or finger operation. When the composition is a cream, it can simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar.
The topical product or composition of the present invention may include an activator as described above. In such a case, the inventive composition must be designed to prevent pre-mature activation of the protected thiol compound prior to use. For instance, the protected thiol compound and the activator may be placed in separate chambers in a dual chamber package, or either of the xe2x80x98hookxe2x80x99 compound or the activator can be placed within shear sensitive (or other induced release) capsules which rupture prior or during use. Alternatively, the protected thiol compound and the activator can be placed in separate packages to enable pre-mixing or sequential application by the consumer. For examples of typical dual chamber packages see PCT Application WO 96/02230, by Unilever PLC, published Feb. 1, 1996. (Herein incorporated by reference.)
Conversely, the cosmetic active of the present invention can be supplied in the purified form, i.e., as a powder, crystal, wax, gum or liquid. The purified cosmetic active could be intermixed with any of the above suitable carriers either prior to or simultaneous to the usage by the consumer. For instance, the purified cosmetic active could be placed within a compartment that is separated from the carrier by a barrier wall. Upon usage, the barrier wall could be broken, disrupted or even removed to enable the purified cosmetic active to come in contact with and inter-mix with the carrier.
The topical composition of the present invention comprises at least one of the above described protected thiol compounds, together with any additional ingredients which are normally to be found in cosmetic treatment compositions for use on hair, skin, or other substrates such as other fibers, textiles, fabrics, or the like. One or more of the protected thiol compounds may be used, the use of two or more being beneficial for example where a combination of cosmetic benefits is wanted, each derivable from a different cosmetic agent species.
While aqueous or aqueous/alcoholic solution based compositions, or possibly organic-based compositions, in which one or more protected thiol compounds are dissolved by solution are preferred, the compositions if desired or appropriate may comprise stable emulsions or dispersions of the one or more functionalized cosmetic agents which are designed to be water insoluble. In both of these cases, conventional means for achieving successful deposition and activation of the active(s) may be required. For instance, an emulsion or a dispersion could be intermixed with a separate solvent solution via a dual phase package to enable solubilization and subsequent activation during usage.
The topical composition according to the invention may include optional benefit materials and cosmetic adjuncts, as long as the benefit materials or the adjuncts do not eliminate or substantially reduce the performance of the organosulfur functionalized cosmetic agent. The additional ingredients may include, for example dyes and coloring agents, fragrances; anionic, cationic, non-ionic, amphoteric or zwitterionic surfactants; buffers, masking fragrances, dispersing agents, stabilizers, cationic polymers, perfumes, non-ionic polymers, anionic polymers, complex coacervates, complex coacervate capsules, metal salts, Lewis acids, buffering agents, particulate thickeners, polymeric thickeners, wax thickeners, oils, emollients, humectants, moisturizers, dyes, dyes and coloring agents, enzymes, antibodies, preservatives, viscosity enhancers, gelling agents, chelators, silicones or other emulsifying agents, and other common adjuvants well known to those skilled in the art.
Nonlimiting examples of anionic lathering surfactants useful in the compositions of the present invention are disclosed in McCutcheon""s Detergents and Emulsifiers, North American edition (1990), published by The Manufacturing Confectioner Publishing Co.; McCutcheon""s Functional Materials, North American Edition (1992); and U.S. Pat. No. 3,929,678, to Laughlin et al., issued Dec. 30, 1975, all of which are incorporated by reference.
A wide variety of anionic surfactants are potentially useful herein. Nonlimiting examples of anionic lathering surfactants include those selected from the group consisting of alkyl and alkyl ether sulfates, sulfated monoglycerides, sulfonated olefins, alkylaryl sulfonates, primary or secondary alkanesulfonates, alkyl sulfosuccinates, acyltaurates, acylisethionates, alkyl glyceryl ether sulfonates, sulfonated methyl esters, sulfonated fatty acids, alkyl phosphates, acylglutamates, acylsarcosinates, alkyl sulfoacetates, acylated peptides, alkyl ether carboxylates, acyllactylates, anionic fluorosurfactants, and mixtures thereof. Mixtures of anionic surfactants can be used effectively in the present invention.
Suitable nonionic surfactants include polyoxyalkylene alcohol surfactants, especially alkyl polyethyleneglycol ethers, alkyl polypropyleneglycol ethers, alkyl polyethyleneglycol esters, and alkyl polypropyleneglycol esters and mixtures thereof.
Suitable amphoteric surfactant components for use in the shampoo composition herein include those which are known for use in shampoo compositions or other personal care cleansing composition, and which contain a group that is anionic at the pH of the shampoo composition. Concentration of such surfactant components in the shampoo composition preferably ranges from about 0.5% to about 20%, preferably from about 1% to about 10%, more preferably from about 2% to about 5% by weight of the composition. Examples of amphoteric surfactants suitable for use in the shampoo composition herein are described in U.S. Pat. No. 5,104,646 (Bolich Jr. et al.), U.S. Pat. No. 5,106,609 (Bolich Jr. et al.), which descriptions are incorporated herein by reference. Examples of amphoteric detersive surfactants which can be used in the compositions of the present invention are those which are broadly described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic water solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate. Examples of compounds falling within this definition are sodium 3-dodecylaminopropionate, sodium 3-dodecylaminopropanesulfonate, sodium laurylsarcosinate, N-alkyltaurines such as the one prepared by reacting dodecylamine with sodium isethionate according to the teaching of U.S. Pat. No. 2,658,072, N-higher alkyl aspartic acids such as those produced according to the teaching of U.S. Pat. No. 2,438,091, and the products sold under the trade name xe2x80x9cMIRANOLxe2x80x9d(trademark) and described in U.S. Pat. No. 2,528,378.
Other amphoteric surfactants, sometimes classified as zwitterionic surfactants, such as betaines can also be useful in the present invention. Such zwitterionics are considered as amphoterics in the present invention where the zwitterionic has an attached group that is anionic at the pH of the composition. Examples of betaines useful herein include the high alkylbetaines, such as cocodimethylcarboxymethylbetaine, cocoamidopropylbetaine, cocobetaine, laurylam idopropylbetaine, oleylbetaine, lauryidimethylcarboxymethylbetaine, lauryidimethyl-alpha-carboxyethylbetaine, cetyldimethylcarboxymethylbetaine, lauryl-bis-(2-hydroxyethyl)carboxymethyl betaine, stearyl-bis-(2-hydroxypropyl)carboxymethyl betaine, oleyldimethyl-gamma-carboxypropylbetaine, and lauryl-bis-(2-hydroxypropyl)-alpha-carboxyethylbetaine. The sulfobetaines may be represented by cocodimethyl sulfopropylbetaine, stearyldimethylsulfopropylbetaine, lauryidimethylsulfoethylbetaine, lauryl-bis-(2-hydroxyethyl)sulfopropylbetaine and the like; amidobetaines and amidosulfobetaines, wherein the RCON(CH2)3 radical is attached to the nitrogen atom of the betaine are also useful in this invention. Most preferred for use herein is cocoamidopropylbetaine.
If desired or as necessary, one or more additional benefit agents may also be included in the compositions of the invention, for example to modify the overall cosmetic benefit or combination of benefits imparted to the substrate treated with the composition. Suitable additional cosmetic benefit agents include the following:
(i) conditioning agents, i.e., materials which impart one or more visual or tactile benefits such as softness, smoothness, shine, non-flyaway, anti-static, ease of dry and/or wet combing, e.g., cationic surfactants, cationic polymers, volatile and/or non-volatile silicones or derivatives thereof, quaternary ammonium salts having at least one long chain alkyl or alkenyl group, protein hydrolysates, quaternized protein hydrolysates, perfluoropolyether materials, fatty alcohols, and mixtures thereof;
(ii) styling/setting/bodying agents, i.e., materials which give enhanced body and fell to the hair or other fibers or enable them to hold a given shape or style, e.g., various polymers, gums and resins, for example adhesive and/or resinous hydrocarbon materials such as per-alk(en)ylhydrocarbon materials, silicone/siloxane gums or resins, waxes, chitosan and derivatives, salts and complexes thereof, and mixtures thereof;
(iii) fiber straightening agents;
(iv) colourants and dyeing agents;
(v) antidandruff agents, e.g., zinc pyridinethione, Octopirox(copyright), climbazole;
(vi) sun-protective materials, e.g. sunscreens, especially UV absorbers;
(vii) hair growth promoters or regulators, e.g. diacylglycerols, glucarolactams, glucarolactones, Minoxidol(copyright);
(viii) moisturizers, e.g. 2-hydroxyalkanoic acids, acid soap and complexes thereof, and other emollients, occlusives, humectants;
(ix) pearlescent and/or opacifying materials;
(x) oils, e.g. silicone oils, oleic acid, hydrocarbons, isopropyl myristate, oleyl alcohol, oleates, squalene, sunflower seed oil, rapeseed oil, other plant derived oils, mineral oil;
(xi) proteins, vitamins, nutrients, stimulants, antiradicals, astringents;
(xii) herb or other plant extracts, essential oils etc.
(xiii) antimicrobial agents, e.g. antibacterial or anti-infestive agents;
(xiv) other adjunct materials commonly used in cosmetic compositions, e.g., buffering and/or pH adjusting agents, perfumes, colorings, preservatives, proteins etc.
(xv) anti-malodor agents as those disclosed to treat post-perm odors in U.S. Pat. No. 5,554,364 and EP 0610892.
(xvi) highly substantive polymers and other moieties including polyethylenimines (PEI""s) such as those included within the Polymin(copyright) series supplied by BASF.
(xvii) metal salts comprising alkaline earth metals such as magnesium and calcium, transition metals such as zinc, manganese and copper, and the group IIIA metals such as Al. The use of these metal salts for hair treatment is disclosed in WO9609030 and WO9703640 where they are claimed to form metal-sulfur bonds with the hair for use in hair styling and restyling. Such metal salts could conceivably be employed to complex and interact with the cosmetic active of the present invention. Such interactions should not interfere too greatly with the performance of the cosmetic actives and could potentially positively influence the performance, i.e., metals could complex with the sulfur atom within cosmetic active and facilitate or induce activation in the form of thiol release.
(xviii) chelating agents including disodium EDTA and tetrasodium EDTA. Chelators could enhance the diffusion and adsorption by binding to and removing metals present in hard water such as calcium and magnesium. Such hard water ions could conceivably complex with certain ionized xe2x80x9chooksxe2x80x9d of the present invention electrostatically and inhibit their solubility.
(xix) hydrotropes such as ammonium xylene sulfate. For instance, if the xe2x80x9chooksxe2x80x9d of the present invention are incorporated within a surfactant matrix, hydrotropes could improve performance by freeing up the xe2x80x9chookxe2x80x9d compounds during dilution to facilitate improved binding to the substrate.
(xx) dispersing aids which may encompass, but are not limited to, non-ionic surfactants, amphoteric surfactants, and ionic surfactants. If the xe2x80x9chooksxe2x80x9d of the present invention are incorporated within a non-aqueous matrix of as an insoluble dispersion, dispersing aids could be utilized to enhance solubilization and subsequent activation.
(xxi) Ion-pair ingredients. For certain ionic xe2x80x9chooksxe2x80x9d of the present invention, compounds could be employed that ion-pair with the xe2x80x9chooksxe2x80x9d including, but not limited to cations, anions, quaternized ammonium compounds, amphoteric compounds, and metals. Such charged species could be utilized to manipulate the diffusion, adsorption and the binding of the xe2x80x9chookxe2x80x9d compounds of the present invention.
(xxii) Drying agents designed to minimize residual levels of water in non-aqueous solvent, including, but not limited to molecular sieves.
The pH of the compositions of the present invention is frequently important in achieving optimized chemisorption of the protected thiol compound. The most suitable pH for a given composition may depend principally on the type and structure of the protecting group as it pertains to activation. For instance, many of the protecting group can be activated for improved performance via pH catalyzed hydrolysis. In these cases, the pH of the composition would need to be such that the molecular xe2x80x98hookxe2x80x99 is not activated prior to usage. As described above, during usage the pH of the composition containing the molecular xe2x80x98hookxe2x80x99 can be manipulated, i.e., via inter-mixing with separate pH activating composition, such that the molecular xe2x80x98hookxe2x80x99 is activated during or immediately prior to usage.
The protecting groups of the present invention are to be used within a pH range from about 1 to about 12, preferably from about 3 to about 11, more preferably from about 4 to about 10. In the cases wherein the protecting group are activated at any of the above pH""s the composition would need to be non-aqueous and essentially free of water or moisture to such a degree that prohibits significant hydrolysis induced activation prior to usage. As such, the water imparted to the composition during usage from the shower, bath or from the wetted substrate could provide the activation required to optimize the resulting chemisorption.
As mentioned above, it has surprisingly been found that certain protecting groups are not activated hydrolytically at pH""s within the above ascribed relevant range while still providing durable benefits on hair. For these compounds, the pH of the composition is irrelevant in as much as the composition pH suits the cosmetically active group, R.
Many of the embodiments of the present invention comprise a silicone composition which includes at least one polysiloxane or silicone resin, at least one linker, and at least one molecular hook. For example, said silicone composition typically imparts improved hair care benefits when added to hair care compositions.
The at least one linker is bound to both a molecular hook and to an atom of a polysiloxane or silicone resin. Preferably the at least one linker is bound to a polysiloxane or silicone resin through a silicon, carbon, oxygen, nitrogen, or sulfur atom, and most preferably to a silicon atom. When more than one linker is present, it is also contemplated that linkers may be bound to a polysiloxane or silicone resin through more than one type of atom, for example through both silicon and carbon atoms.
Therefore, in one embodiment the present invention comprises at least one polysiloxane or silicone resin having the formula:
MaMxe2x80x2bDcDxe2x80x2dTeTxe2x80x2fQg
where the subscripts a, c, d, e, f and g are zero or a positive integer, subject to the limitation that the sum of the subscripts b, d and f is one or greater, where M has the formula:
R13SiO1/2,
Mxe2x80x2 has the formula:
(Zxe2x80x94X)R22SiO1/2,
D has the formula:
R32SiO2/2,
Dxe2x80x2 has the formula:
(Zxe2x80x94X)R4SiO2/2
T has the formula:
R5SiO3/2,
Txe2x80x2 has the formula:
(Zxe2x80x94X)SiO3/2,
and Q has the formula SiO4/2, where each R1, R2, R3, R4, R5 is independently at each occurrence a hydrogen atom, C1-22 alkyl, C1-22 alkoxy, C6-14aryl, and C6-22 alkyl-substituted aryl, and C6-22 aralkyl which groups may be halogenated, for example, flourinated to contain fluorocarbons such as C1-22 fluoroalkyl; Z, independently at each occurrence, represents the molecular hook; and X, independently at each occurrence, represents the linker. The term xe2x80x9calkylxe2x80x9d as used in various embodiments of the present invention is intended to designate both normal alkyl, branched alkyl, aralkyl, and cycloalkyl radicals. Normal and branched alkyl radicals are preferably those containing from 1 to about 12 carbon atoms, and include as illustrative non-limiting examples methyl, ethyl, propyl, isopropyl, butyl, tertiary-butyl, pentyl, neopentyl, and hexyl. Cycloalkyl radicals represented are preferably those containing from 4 to about 12 ring carbon atoms. Some illustrative non-limiting examples of these cycloalkyl radicals include cyclobutyl, cyclopentyl, cyclohexyl, methylcyclohexyl, and cycloheptyl. Preferred aralkyl radicals are those containing from 7 to about 14 carbon atoms; these include, but are not limited to, benzyl, phenylbutyl, phenylpropyl, and phenylethyl. Aryl radicals used in the various embodiments of the present invention are preferably those containing from 6 to 14 ring carbon atoms. Some illustrative non-limiting examples of these aryl radicals include phenyl, biphenyl, and naphthyl. An illustrative non-limiting example of a halogenated moiety suitable for R1-5 groups is trifluoropropyl.
The polysiloxanes or silicone resins of the present invention are typically prepared by the hydrosilylation of an organohydrogen silicone having the formula:
MaMHDcDHdTeTHfQg
where the subscripts a, c, d, e, f and g are zero or a positive integer, subject to the limitation that the sum of the subscripts b, d and f is one or greater; where M has the formula:
R13SiO1/2,
MH has the formula:
R23-hHhSiO1/2,
D has the formula:
R32SiO2/2,
DH has the formula:
H2-iR4iSiO2/2
T has the formula:
xe2x80x83R5SiO3/2,
TH has the formula:
HSiO3/2;
and Q has the formula SiO4/2, where each R1, R2, R3, R4, R5 is independently as defined above.
Hydrosilylation is typically accomplished in the presence of a suitable hydrosilylation catalyst. The catalyst preferred for use with these compositions are described in U.S. Pat. Nos. 3,715,334; 3,775,452; and 3,814,730 to Karstedt. Additional background concerning the art may be found at J. L. Spier, xe2x80x9cHomogeneous Catalysis of Hydrosilation by Transition Metals, in Advances in Organometallic Chemistry, volume 17, pages 407 through 447, F. G. A. Stone and R. West editors, published by the Academic Press (New York, 1979). Persons skilled in the art can easily determine an effective amount of platinum catalyst. Generally, an effective amount ranges from about 0.1 to 50 parts per million of the total organopolysiloxane composition.
The organohydrogen silicone compounds that are the precursors to the compounds of the present invention may be prepared by the process disclosed in U.S. Pat. No. 5,698,654 herewith specifically incorporated by reference. The ""654 patent discloses a sequential catalysis of the ring. opening polymerization of cyclic organosiloxanes using a base catalyst that can be neutralized by a subsequent redistribution and condensation catalyst such as a Lewis acid catalyst, preferably a phosphonitrilic compound, that permits the rapid synthesis of functionalized and poly-functionalized silicone copolymers.
It is to be noted that as pure compounds the subscripts describing the organohydrogen siloxane precursor and the hydrosilylation adduct of the present invention are integers as required by the various rules of chemical stoichiometry. As mixtures of compounds that are described by these formulas the subscripts will assume non-integral values, for the mixtures. The restrictions on the subscripts heretofore described for the stoichiometric subscripts of these compounds are for the pure compounds, not the mixtures.
In specific embodiments of the present invention, the silicone composition typically comprises at least one compound of the following formulas, (I), (II), (III), (X), (XI), and 
where each R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, and R36 is independently at each occurrence a hydrogen atom, C1-22 alkyl, C1-22 alkoxy, C1-22 alkenyl, C6-14 aryl, and C6-22 alkyl-substituted aryl, and C1-22 aralkyl which groups may be halogenated, for example, flourinated to contain fluorocarbons; Z, independently at each occurrence, represents a molecular hook; and X, independently at each occurrence, represents a linker; wherein xe2x80x9cmxe2x80x9d in each formula has a value in a range between about 0 and about 13,000, preferably about 0 and about 1000, more preferably between about 1 and about 250, still more preferably between about 5 and about 150, even more preferably between about 10 and about 100, and most preferably between about 20 and about 50; xe2x80x9cnxe2x80x9d in each formula has a value in a range between about 0 and about 13,000, more preferably between about 0 and about 50, more preferably between about 1 and about 20, still more preferably between about 2 and about 10, and most preferably between about 2 and about 5; xe2x80x9cm+nxe2x80x9d in each formula has a value in a range between about 1 and about 13,000, preferably between about 3 and about 70, more preferably between about 5 to about 50, and most preferably between about 15 and about 50; xe2x80x9cqxe2x80x9d has a value of at least one and xe2x80x9cp+qxe2x80x9d has a value of at least 3, preferably in the range of 3-20, more preferably in the range of 3-10, and most preferably in the range of 3-6. The polysiloxane or silicone resin typically has a molecular weight ranging from about 100 to about 1,000,000, preferably from about 250 to about 50,000, more preferably from about 500 to about 25,000, and most preferably from about 500 to about 7,000. The at least one polysiloxane or silicone resin typically has a viscosity in a range between about 20 centipoise and about 2,500,000 centipoise (about 0.02 to about 2500 Pas).
The number of Xxe2x80x94Z moieties on a polysiloxane or silicone resin in the composition is at least one. In preferred embodiments the average number of Xxe2x80x94Z moieties on a polysiloxane or silicone resin is between about 1 and about 100, more preferably between about 1 and about 20, still more preferably between about 1 and about 6, and most preferably between about 3 and about 6.
In one embodiment of the present invention a polysiloxane- or silicone resin-containing composition comprises a preponderance of a specific linear, branched, cross-linked, or cyclic polysiloxane or silicone resin. In other embodiments a polysiloxane- or silicone resin-containing composition comprises a mixture of polysiloxanes and/or silicone resins which may include linear, branched, cross-linked, and cyclic species. Also, suitable compositions may comprise one or more polysiloxanes and/or silicone resins which may contain adventitious amounts of other species, for example arising during the synthesis process for said polysiloxanes and/or silicone resins, for example at a level of about 0.0001 wt. % to about 5 wt. % based on total silicon-containing species. In illustrative examples suitable compositions may contain adventitious amounts of D4, or species containing Sixe2x80x94H, Sixe2x80x94OH, and/or Sixe2x80x94O-alkyl bonds. 
The molecular hook may be a heterocyclic pyridinium compound (IV), a heterocyclic triazinium (V), or a heterocyclic pyrimidinium compound (VI):
wherein Y represents optional substituents on the heterocyclic ring or ring system, X represents the linker, Qxe2x88x92 represents a counterion, and A is defined below. 
Optional substituents, Y, which can be present on the heterocyclic ring or ring system can be selected from hydrogen or electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between xe2x88x921.0 and +1.5 comprising carbon-linked groups of the classes defined as A1, A2, A3, and A4; S-linked groups including SA1, SCN, SO2A1, SO3A1, SSA1, SOA1, SO2NA1A2, SNA1A2, S(NA1)A2, SA1(NA2), SONA1A2; O-linked groups including OA1, OCN, ONA1A2; N-linked groups including NA1A2, NA1A2A3+, NA1OA2, NA1SA2, NCO, NCS, NO2, Nxe2x95x90NA1, Nxe2x95x90NOA1, NA1CN, Nxe2x95x90Cxe2x95x90NA1, NA1NA2A3, NA1 NA2NA3A4, NA1Nxe2x95x90NA2; other miscellaneous groups including CONA12, CONA1COA2, C(xe2x95x90NA1)NA1A2, CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of the optional substituents via a ring system; Hal is fluorine, chlorine, bromine, or iodine.
A, A1, A2, A3, and A4 each represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or polycyclic aliphatic, mono- or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0 to 15 heteroatoms, especially oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), silicon (Si) and can incorporate one or more substituents including, but not limited to, poly or perfluoro substitution.
The counterion, Qxe2x88x92, can include halides, borates, phosphates, tosylates, mesylates, triflates, and other counterions known to those skilled in the art.
The linker comprises a C1-C50 alkyl, aryl, or alkylaryl group, or C1-C50 heteroaryl group containing one or more heteroatoms, and is optionally functionalized. Optional functionalization on the linker includes ketones, alkoxys, esters, amides, trifluoromethyl, halogens, nitriles and other polar functional groups known to those skilled in the art. The linker is typically derived from a linker precursor which comprises a linker bound to a leaving group (L). Illustrative leaving groups include halides such as chloride, bromide and iodide; tosylate, mesylate, phosphate; cyclic leaving groups (that is, those in which the leaving group remains bound in the linker) such as epoxy or other cyclic leaving group containing at least one heteroatom; and other leaving groups known to those skilled in the art. Preferred leaving groups are bromide and iodide, with iodide being particularly preferred.
In synthesis, the leaving group is replaced by a molecular hook, so that the linker becomes bound to a molecular hook. In one embodiment the at least one linker precursor may be combined with the at least molecular hook before combining with a polysiloxane or silicone resin. In a particularly preferred embodiment the at least one linker precursor may be combined with a polysiloxane or silicone resin before combining with the at least molecular hook.
Typically, the linker precursor has the formula (VII)
xe2x80x94Dxe2x80x94Ar(Y)nxe2x80x94CH2xe2x80x94Lxe2x80x83xe2x80x83(VII)
is wherein D comprises a group bound to a polysiloxane or a silicone resin; xe2x80x9cArxe2x80x9d is an aromatic or heteroaromatic group, optionally substituted with one or more substituents; xe2x80x9cYxe2x80x9d is a substituent; xe2x80x9cLxe2x80x9d is as defined above; and xe2x80x9cnxe2x80x9d has a value between zero and the number of free valence sites on the aromatic or heteroaromatic ring. Non-limiting examples of suitable aromatic and heteroaromatic groups in linkers include phenyl, biphenyl, toluyl, naphthyl, pyridyl, quinolyl, triazinyl, pyrimidyl, pyridazinyl, furyl, furoyl, and thienyl. Illustrative examples of substituents (Y) which may be bound to said aromatic or heteroaromatic group include C1-22 straight chain, branched, cycloaliphatic, or aralkyl; C6-14 aryl; fluoro, chloro, bromo, iodo, nitro, nitroso, nitrile, trifluoromethyl, trifluoropropyl, alkyloxycarbonyl, alkylcarbonyl, alkylamido, alkyl ether, aryl ether, and similar electron-withdrawing, electron-donating, and electron-neutral groups. The xe2x80x9cDxe2x80x9d group may comprise a straight chain, branched, cycloaliphatic, or aralkyl group which optionally may contain a functional group, said functional group being bound to D in a pendent position or separating D from the aromatic or heteroaromatic group, or separating D from a polysiloxane or a silicone resin, or in more than one of these positions. Illustrative examples of D groups include C1-22 alkyl and preferably C2-3 alkyl. Illustrative examples of functional groups which may be present with D include carbonyl, alkylcarbonyl, oxycarbonyl, alkyloxycarbonyl, nitrile, amido, alkylamido, trifluoromethyl, and halogen, such as chloro, bromo, and/or fluoro. Preferred examples of linkers are shown in formulas (VIII) and (IX): 
Silicone-containing compositions comprising at least one polysiloxane or silicone resin, at least one linker, and at least one molecular hook typically impart cosmetic and other benefits in applications such as hair care (for example durable hair care benefit), textile care, cosmetics, oral care, and animal care.
In order that those skilled in the art will be better able to practice the invention, the following examples are given by way of illustration and not by way of limitation.
Characteristics
The protected thiol compounds of the present invention, when applied to a amino acid based substrate, have improved uptake levels and reduced levels of fade or removal. That is the thiol functional groups demonstrate improved attachment of the functional is group, R, to the amino acid based substrate and longer lasting attachment than alternative reactive technologies. These benefits are demonstrated without requiring addition steps of reducing or oxidizing the substrate which typically are required in the art to achieve durable cosmetic benefits.
Reduction as defined herein comprises chemical compositions and treatments that induce the nucleophilic cleavage of disulfide bonds in keratin substrates resulting in the formation of free thiol groups in the form of cysteinyl amino acid residues. Reduction is employed in several commercial. products and processes including the permanent-waving of human hair, human hair straightening, human hair depilation, and in the dyeing of wool with fiber reactive dyes. Several compounds and processes known to induce keratin reduction include (i) low molecular weight thiols such as thioglycolic acid, thiolactic acid, cysteine, thioglycerol, thioglycolic hydrazide, thioglycolamide, and glycerol monothioglycolate, (ii) sulfides such as salts of hydrogen sulfide, (iii) high temperature and alkali wherein the keratin is heated to around 100xc2x0 C. or above by a heating source or steam and wherein the keratin can be contacted with an alkaline solution, (iv) cyanide such as the salts of hydrogen cyanide, (v) phosphines such as trihydroxymethyl phosphine or its precursor, tetrahydroxymethyl phosphonium chloride, (vi) other miscellaneous reducing agents such as borohydride, dithionite, hydrosulfite, and sulfoxylate and (vii) combinations thereof. Reduction as defined herein generally refers to the above processes and compositions which reduce greater than 10% of the disulfide bonds in the keratinaceous substrate. The relative quantities of reduced versus unreduced keratin fiber depend on the type of reducing agent, its concentration (or degree of application in the case of heat), the solution-to-hair ratio, pH of the reaction medium, time of reaction, fiber diameter, and the condition of the hair. A more detailed discussion on disulfide reduction can be found in the article by Gershon et al. (Gershon, S. D.; Goldberg, M. A.; Rieger, M. In Cosmetics Science and Technology, Sagarin. E. , eds., pp. 583-627. Interscience, New York (1963)).
Oxidation as defined herein comprises chemical compositions and treatments that induce the oxidative cleavage of disulfide bonds in keratin substrates resulting in the formation of sulfonic acid groups in the form of cysteic acid amino acid residues. Oxidation is employed in several commercial products and processes including the bleaching of human hair, permanent dyeing of human hair with oxidation dyes, and in the dyeing of wool with fiber reactive dyes. Hydrogen peroxide is the principle oxidizing agent used in most oxidizing compositions and is delivered liberally to the substrate as a 3 to 12% solution which may be alkaline. Persulfates, in the form of their sodium potassium and ammonium salts, may also be used to be mixed with the hydrogen peroxide just before use. Other ingredients that may be additionally included in the composition include sodium percarbonate, sodium perborate, magnesium perborate, magnesium dioxide and barium binoxide. Oxidation as defined herein generally refers to the above processes and compositions which degrade greater than 10% of the disulfide bonds in the keratinaceous substrate. A more detailed discussion on disulfide oxidation can be found in the articles by Zahn and Robbins (Zahn, H. J. Soc. Cosmet. Chem. 17:687 (1966); Robbins, C.; Kelly, C. J. Soc. Cosmet. Chem. 20:555 (1969)).
Both reduction and oxidation of amino acid based substrates lead to irreparable damage to the substrate by virtue of their destructive chemical reactions. For instance, both reduction and oxidation result in disulfide bond cleavage which has been shown to significantly reduce the wet tensile properties of human hair through 30% extension (Clarence Robbins book: Chemical and Physical Behaviour of Human Hair). Also, reduced hair has been shown to be less rigid in the wet state than unreduced hair (Bogaty, H. J. Soc. Cosmet. Chem. 18:575 (1967)) and the wet bending stiffness and wet stretching stiffness were demonstrated to decrease on oxidized hair (Robbins Book). Furthermore, reduced hair has been shown to exhibit increased frictional resistance (Schwartz, A.; Knowles, D. J. Soc. Cosmet. Chem. 14:455 (1963)) which is evidence of imparted damage to the hair. These demonstrated destructive chemical interactions with keratin have been shown to translate into keratin that is drier, more brittle to the touch, more porous, weaker and which tangles more easily (The Science of Hair Care, by Charles Zviak).
Processes for Preparing the Protected Compounds
The compounds of the invention can be prepared by any of a number of procedures is known to those skilled in the art. Several nonlimiting examples are described herein below.
Heterocyclic Protecting Groups
Alkylthio substituted pyridines can be prepared by reaction of halopyridines with a variety of thiols in the form of metal salts [Takahashi, Saikachi, Akai, J. Pharm. Soc. Japan, 1943, 63, 153; Adams, Ferreti, J. Am. Chem. Soc., 1959, 81, 4927]. Another method of preparation involves alkylation of pyridinethiols [Marckwald, Klemm, Trabert, Ber., 1900, B33, 1156; Forrest, Walker, J. Chem. Soc., 1948, 1939].
Alkylthio substituted pyrimidines can be prepared by alkylation of mercaptopyrimidines [Southon, Pfeiderer, Chem. Ber., 1978, 111, 982; A. G. Geigy, Chem. Absir., 1969, 70, 68418] or directly from halogenopyrimidines [Semga, Ichiba, Kanazawa, Nishigaki, J. Heterocyclic. Chem., 1982, 30, 610].
Alkylthio substituted pyrazines can be prepared from halogenopyrazines and appropriate sodium (or potassium) alkyl thiolate at elevated temperatures [Konakahara, Y. Takagi, Bull. Chem. Soc. Japan, 1960, 80, 349]. The alternative method is alkylation of mercaptopyrazines [A. Albert, G. B. Barlin, J. Chem. Soc., 1962, 3129].
Alkylthio substituted pyridazines can be prepared by treatment of halopyridazines with a thiol in the form of its alkali salt or with a thiol in the presence of base [Druey, K. Meier, K. Eichenberger, Helv. Chin. Acta, 1954, 37, 121; M. Fujisaka, Y. Neno, H. Shinobara, E. Imoto, Bull. Chem. Soc. Japan, 1964, 37, 1107; T. Horie, K. Kinjo, T. Ueda, Chem. Pharm. Bull., 1962, 10, 580]. Alkylation of pyridazinethiones and pyridazinethiols as well as some other methodologies are also published. [M. Tisler and B. Stanovnik xe2x80x9cPyridazines and their Benzo Derivativesxe2x80x9d, in xe2x80x9cComprehensive Heterocyclic Chemistryxe2x80x9d, 1984, Pergamon Press, Ltd.; M. Tisler and B. Stanovnik xe2x80x9cSultur Compounds of Pyridazinesxe2x80x9d, in xe2x80x9cThe Chemistry of Heterocyclic Compoundsxe2x80x9d, 1973, John WileyandSons, Inc.]
For the alkylthiol substituted triazines and tetrazines, a comprehensive review on the synthesis of these compounds is found in the literature. [M. Tisler and B. Stanovnik, J.Het. Chem., 1971, 785; Reissert and Grube, Chem. Ber., 42, 1909, 3720; Gompper and Schoenafinger, Chem. Ber., 112, 1979, 1529; Arndt, Eistert, Chem. Ber., 60, 2602, 1927; Grundmann et al, J. Org. Chem., 23, 1958, 1522; Cristescu, Panaitescu, Pharmazie, 17, 1962, 209; H. Neunhoeffer, H. Hammann, Tet. Lett., 24, 1983, 1767; J. L. Johnson, B. Whitney, L. M. Leslie, J. Het. Chem., 17, 1980, 501; S. C. Fields, M. H. Parker, W. R. Erickson, J. Org. Chem., 1994, 8284.]
The six membered O, N, and/or S containing heterocyclics with Cxe2x95x90O, Cxe2x95x90S or Cxe2x95x90C exocyclic groups can be prepared from halogen derivatives of corresponding heterocycles and thiols. [Tominaga, A. Ushirogochi, Y. Matsuda, J. Het. Chem., 24, 1987, 1557; Y. Tominaga, et al, Chem Pharm, Bull., 32, 3384, 1981; L. Adelfang, J. Org. Chem., 31, 2389, 1966; L. W. Singh, H. Junjappa, Synthesis, 5, 531, 1985; W. D. Rudorf, R. Schawrz, Tet. Lett., 28 4267, 1987; B. Deb, H. Ila, et al, Synthesis, 10, 893, 1987.]
Alkylthio substituted pyridinium derivatives can be prepared by quaternization of the corresponding pyridine alkyl thioethers and other methods. [Yamada, et al, J. Org. Chem., 42, 2180, 1977; M. Yamada, et al, J. Chem. Soc., Chem. Comm., 179, 1979; T. Sakakibara, Y. Watabe, M. Yamada, R. Sudoh, Bull. Chem. Soc. Jpn, 61, 247, 1988.]
Alkylthio substituted xanthenes can be prepared from thiols and xanthene with a suitable leaving group [K. J. Divakar, C.B. Reese, et. al., J. Chem. Soc., Perkin Trans. 1, 1990 (6), 1753.]
Alkylthio substituted pyrimidinium derivatives can be prepared by quaternization of the corresponding pyrimidine alkylthioethers and other methods. [Deichmeister, Platoshkiin, Khim. Geterosicl. Soedin., 1, 1961, 333; Brown, England, J. Chem. Soc. C, 1971, 2507; Ueda, Ohtsuka, Chem. Pharm. Bull., 21, 1973, 1451.1.]
Alkylthio substituted pyrazinium derivatives can be prepared by quaternization of the corresponding pyrimidine alkyl thioethers and other methods. [Barlin, Benbow, J. Chem. Soc., Perkin Trans. 2, 1975, 1385; Honz, et al, Tetrahedron, 26, 1970, 2305; B. Geutsen et al, Tetrahedron, 1989, 6519; S. Batori, A. Messmer, J. Het. Chem., 1990, 1673.]
Alkylthio substituted furans can be prepared from the corresponding furan thiols and alkyl halides. [Gorzynski, D. Rewicki, Liebigs Ann. Chem., 1986, 625; P. G. McDougal, Y-I Oh, Tet. Lett., 27, 139, 1986; R. Tanikaga, et al, J. Chem. Soc., Chem. Comn., 1106, 1981; H. Gotthatdt, C. M. Weisshuhn, K. Dorhofer, Chem. Ber., 111, 3336, 1978; R. Adams, A. Ferretti, J. Am. Chem. Soc., 81, 4927, 1959; A. Ferretti, G. Tesi, Chem Ind., p. 1987, 1964; L. M. Yagupoiskii, N. V. Kondratenko, V. P. Sambur, Synthesis, 721, 1975; B. L. Feringa, et al, Synthesis, 316, 1988; S. P. Tanis, D. B. Head, Tet. Lett., 25, 4451, 1984.]
Alkylthio substituted pyrroles can be prepared by S-alkylation of 2- and 3-pyrrolethiols under standard base-catalyzed conditions. [K. Olsen, H. R. Snyder, J. Org. Chem., 30, 184, 1965; S. Apparao; H. Ila, H. Junjappa, Synthesis, 65, 1981; M. Cardellini et al, Synthesis, 1980, 886; A. K. Gupta, H. Ila, et al, Synthesis, 141, 1989; S. Gronowitz, R. Kada, J. Het. Chem., 1041, 1984; M. Colonna, M. Polni, Gazz. Chim. Ital., 116, 449, 1986; H. Kojima, H. Inoue, et al, Chem. Lett., 1499, 1989; Y. Tominaga, et al, J. Het. Chem., 26, 477, 1989.]
Alkylthio substituted thiophenes can be prepared by reacting the alkali salts of thiophene thiols with aliphatic halogen compounds. [Thomas, G. Singh, H. Ila, H. Junjappa, Tet. Lett., 30, 3093, 1989; W.-D. Rudorf, A. Schierhorn, M. Augustin, J. Prakt. Chem., 321, 1021, 1979; J. Cymerman-Craig, J. W. Loder, Org. Synth. 667, 1963; J. Cymerman-Craig, J. W. Loder, J. Chem. Soc., 237, 1954; E. J. Smutny, J. Am. Chem. Soc., 91, 208, 1969.]
Alkylthio substituted pyrazoles, the 3- and 5-derivatives, can be prepared by the alkylation of the corresponding pyrazolethiones [Michaelis, Lachwitz, Chem. Ber., 1910, 43, 2106; Michaelis, Ann., 1908, 283].
Alkylthio substituted isoxazoles can be prepared by alkylating the thio group at the 3 position of isoxazoles [A. Thuiller and J. Vialle, Bull.Soc. Chim. Fr., 1959, 1398; W. D. Rudrorf and M. Augustin, J. Prakt. Chem., 1978, 320, 585;: K. Tomita, S. Sugai and M.Saito, Chem. Pharm. Bull., 1979, 27, 2415; S. Sugai and K. Tomita, Chem. Pharm. Bull., 1980, 28, 552].
Alkylthio substituted isothiazoles can be prepared by alkylating both 3- and 5-mercaptoisothiazoles [K. R. H. Wooldridge, Adv. Heterocycl. Chem., 1972, 14, 1; B. Torretta, G. Ronsisvalle, E. Bousquet, F. Guerrera and M. A. Siracusa, Gazz. Chim. Ital., 1980, 133;: K. Gewald, W. Radke and U. Hain, J. Prakt. Chem., 1980, 322, 1021].
Alkylthio substituted triazoles can be prepared from the corresponding thiotriazoles by S-alkylation with various alkyl bromides [M. A. Weaver, R. R. Giles, Ger. Pat., 1970, 1,919,045; J. Heindi, E. Schroeder, H. W. Kelm, Eur. J. Med. Chem.xe2x80x94Chim. Ther., 1975, 10, 121.].
Alkylthio substituted 1,2,4-oxadiazoles can be prepared from the corresponding halogen oxadiazoles and thiols. [M. Paton, D. G. Hamilton, Tet. Lett., 24, 5141, 1983; D. J. Greig, et al, J. Chem. Soc., Perkin Trans., 607, 1987; Sumitomo Chem Ind KK, Japan Patent, 1005072 (J6-1005072), 86-05143, 1986.]
Alkylthio substituted 1,2,4-thiadiazoles can be prepared via dipotassium cyanodithioiminocabonate followed by alkylation [W. A. Thaler and J. R. McDivitt, J. Org. Chem., 1971, 36, 10;: Badische Anilin und Soda-Fabrik A.-G., Br. Pat. 1 116198 (1968), (Chem. Abstr., 1968, 69, 86995)].
Alkylthio substituted pyrazolium derivatives can be prepared by reaction of the corresponding alkylthiopyrazoles with alkyl halides. [Michaelis, Justus Lieb. Ann. Chem., 331, 1904, 230; v. Auwers, Bergmann, Justus Lieb. Ann. Chem., 472, 1929, 310; Michaelis, Justus Lieb. Ann. Chem., 361, 1908, 270; K. Hartke, X.-P. Popp, Arch. Pharm, 1994, 385.]
Alkylthio substituted triazolium derivatives can be prepared from halogen derivatives of the corresponding triazoles and lithium thiolates [M. Begtnup, Bull. Soc. Chim. Belg., 1988, 573].
Alkylthio substituted azepines can be obtained from the corresponding halogen derivatives [W. Steglich, H. Bauek, B.M. Grosse, R. Leschke, T. Josten, J. Klein, J. Heterocycl. Chem., 1990, 107].
Alkylthio substituted thiepinium derivatives can be prepared from the corresponding thiepins and an alkylation agent [H. Hofmann, A. Molnar, Tetrahedron Lett., 1977, 1985; H. Hofmann, A. Molnar, C. Gottfent, Liebigs Ann. Chem., 1983, 425; H. Hofmann, H. Fisher, M. De Vries, Z. Naturforsch, Teil B, 1990, 1573].
Synthesis routes for heterocyclic protected thiol compounds are exemplified by the following non-limiting examples: